STRUCTURAL AND FUNCTIONAL-CHANGES IN DIABETIC GLOMERULOPATHY

Diabetic nephropathy is characterized by glomerular basement membrane thickening and mesangial expansion. Immunohistochemical studies of dia betic kidneys showed an increased collagen type IV synthesis and depos ition in the mesangial matrix, while the glomerular heparan sulfate pr oteoglycan content was decreased. In nodular glomerulosclerosis massiv e deposition of collagens III and VI appears, possibly indicating irre versibility of the pathological process. These structural changes seem to be the underlying cause for the alterations of renal functions lik e persistent albuminuria and proteinura. In a recent study significant glomerular infiltration by macrophages at all stages of glomeruloscle rosis was observed. The pathogenesis of the multitude of cellular, str uctural, and functional abnormalities in diabetic nephropathy is likel y to be multifactorial, involving chronic hyperglycemia as well as gen etic determinants. In vitro studies with cultured glomerular cells hav e indicated that hyperglycemia induces transforming growth factor beta , a matrix-producing cytokine. The hyperglycemia-induced cytokine prod uction may involve protein kinase C activation and/or the formation of advanced glucosylation end products. The elucidation of the pathogene sis of diabetic nephropathy may suggest new ways for therapeutic inter ventions.